DOSSIER

1. DOSSIER ON DRUG SAFETY
About the Company
QUADRI SULEIMAN  LANZULE INC  4/3/2016
Lanzule is a pharmaceutical servicing company. We are involved in
Pharmacovigilance, Drug discovery and Drug Development. Lanzule was
incorporated 21st
of October, 2015. Our offices are located in Abuja, Nigeria and London,
UK, we would report to Regulatory Authorities in Nigeria, Ghana, EU, and the USA.
Services
General Pharmacovigilance, medical device vigilance.
The Detailed Description of the Pharmacovigilance System (DDPS) is being
replaced by the requirement for a Pharmacovigilance System Master File (PSMF).
The Old System (DDPS): The old style document was defined within Volume 9a of
the Rules Governing Medicinal Products in the EU (drug safety regulations) which
detailed responsibilities for Marketing Authorizations applicants and holders, plus
the Competent Authorities in each member state who would deal with them.
Volume 9A was specific on the elements of drug safety that should be included in
the DDPS, but in general left it to the Applicant to provide the detail.
Although the DDPS will be phased out completely for all authorisations in 2015,
while the DDPS is still being used, its method of working is now driven by Good
Vigilance Practice (GVP). The EU is currently in an interim state and hence DDPS is
still being used.
The New System: Pharmacovigilance System Master File (PSMF) - Since 2012 the
new regulations, from which GVP is derived affects:
1. All new applications for Marketing Authorisation within the EU.
2. All existing Marketing Authorisations.
Instead, new applications and applications for variation must include summaries of
the drug safety systems, details of the appointment of the EU QPPV – and details
of where the PSMF is located for inspection. All pharmaceutical companies
marketing products in the EU are affected as all Marketing Authorisations will
eventually need to be migrated over to the new system by July 2015 or risk having

2.  DOSSIER ON DRUG SAFETY
Lanzule Inc  Page 1
DOSSIER ON
DRUG SAFETY
About the Company
Drug Discovery, Drug Development and
Pharmacovigilance.
All new drugs must be evaluated for any
toxicity during their development; so
safety profiles could be established. Once
the basic safety data has been
established, limited doses will be given to
volunteers in clinical trials. Should the
safety profile be acceptable, and
approved by a regulatory body, the drug
would be sold for use in the general
patient population.
Safety assessment of a drug (medicine)
does not stop with issue of a Marketing
Authorisation Approval (MAA).
Pharmacovigilance activities do reveal
insights into hazards associated with
medicinal products, reporting adverse
drug reactions i.e. Drug Drug Interactions
(DDI). Pharmaceutical toxicologists
evaluate toxicity of drugs in the
development programme.
Drug Safety.
Drugs provide significant benefits to
human health. A good number of drugs
are known to cure, stabilise and prevent
diseases. Just as these drugs have helped
improve living conditions of people, they
have undergone rigorous screening and
checks before they are marketed for safe
human consumption. Drug safety involves
assessment, understanding and
prevention of adverse effects of an
investigational Medicinal Product (IMP).
IMP can be active pharmaceutical
substance in the form of drugs, medical
devices and vaccines as defined by
Medicine and Health Products Regulatory
Agency (MHRA) under European Union
Directive 2001/20/EC(1). Marketing
approval of drugs are allowed only if the
benefits outweigh their risks, and in the
U.K the main governmental body
responsible for drug Approval is the
(MHRA) and its U.S.A equivalent is the
Food Drug Administration (FDA)7). The
earliest stages of drug development
begins with preclinical studies where;
extensive research is done in vitro and ex
vivo (cell tissues), before moving onto in
vivo animal studies. The animal studies
should be done in GLP labs, 3R’s and
Animal Scientific Protection Acts 1986.
Preclinical studies most important goal is
to determine safety profiles in short term
and long term treatment effect of IMP (7).
Other data collated from preclinical
studies are the efficacy, pharmacokinetics,
pharmacodynamics and toxicity of such
IMP’s (5).

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Approved Clinical Trial Authorisation
must be received in writing from the
MHRA and Research Ethics Committee
(REC) before human clinical trials can
proceed (4). Collated data gives
researchers a prediction of safe starting
doses in clinical trials. Clinical trials are
also known as test in Man and usually
consist of four stages.i.e. Phase I – IV. The
starting dose can be determined using the
NOAEL from preclinical studies and
uncertainty factor based on surface area
ratios. Phase I – III trials are pre-marketing
studies and can take up to 10 years or
more whilst the Phase IV is usually a post
marketing research (2).
 Phase I trials are single doses of an IMP
given in increasing amounts usually done
in healthy subjects numbering about 20 -
100 and endpoints are to determine
safety, tolerability, pharmacokinetic
effects and pharmacodynamic effects.
 Phase II trials are done in patients of
targeted diseases numbering about 100 -
1000 and endpoints are determined if it is
really safe, pharmacokinetic and
pharmacodynamic effects giving an
indication of how to design the phase III
stage.
 Phase III trials are done in patients of
targeted diseases numbering about 1000
– 10000 and its used to build on the data
gained from the first two phases of trials
and at this stage results are extrapolated
to the general Public. At the end of this
stage, Marketing Authorisation
Application of new drug application are
applied for approval from MHRA or FDA
as the case may be, it becomes a Phase IV
trial candidate.
 Phase IV trials are post marketing studies
in patients of targeted diseases
numbering from tens of thousands
upwards. At this stage the IMP is
compared to any drugs with similar effects
or properties to determine which is better.
See Appendix 1 for flow chart in the development
of a drug.
A safety and efficacy Update report of all
information about the study drug (IMP) should
be recorded at intervals, which can be supplied to
all investigators and ethic committees (5).
Pharmacovigilance takes off after the post
marketing stage which watches out for any
Adverse Reactions (ADR) of the new medicine.
Pharmacovigilance plays major roles in the deeper
understanding of benefits and risks of medicines
thereby ensuring drug safety throughout the
lifecycle of a new medicine. (8). Adverse events
(AE’s) when reported by study teams during post
marketing trials can be serious adverse events
(SAE). All SAE’s should be reviewed and
investigators should report to the sponsor or
Manufacturing Authorisation Holder.i.e.
pharmaceutical company/manufacturer. All cases
of Suspected Unexpected Serious Adverse
Reactions (SUSAR) of IMP’s new medicines must
be reported to MHRA (9) in the UK or the FDA in
the U.S, the REC (10), the Sponsors and its QA
departments. All fatal life threatening SUSARs
must be reported within 7 calendar days (6) to the
MHRA whilst other SUSARs should be reported to
MHRA within 15 calendar days.
See Appendix 2 for workflow of
Pharmacovigilance.
All documents should be kept safe and archived
for future references and Qualified Person should

4.  DOSSIER ON DRUG SAFETY
Lanzule Inc  Page 3
ensure that the SOP (3) is followed; the IMP meets
the EU GMP requirements or equivalents. The
process of drug safety involves a large amount of
information that cannot easily be gathered, it
requires a lot of expertise and experience that can
be archived through continuous exposures to
research and clinical trials.
Safety Practices
Data Entry onto company database.
Data review on company database.
Review of safety information from clinical
trials and post marketed products.
Electronic reporting of safety cases to
regulatory Agencies.
Paper reporting of ADRs to Regulatory
Authorities.
Compliance matrices for client and
company review.
Literature searching for ADRs.
Writing safety summaries for literature
articles.
Writing sections of Periodic Safety
Update Reports.
Assessing adverse reactions for potential
signals.
Coding adverse events.
Producing summary safety tables for
client review.
Preparation and training for regulatory
inspections.
Follow up of safety cases to closure.
MedDRA coding.
Adverse event case files production and
archiving.
Understanding and helping with
determining ADR reportability.
SOP review and writing.
Accompanying audits to clients and SOP
review.
Attendance at meetings concerning
possible client work.
On site client work involving any of the
above.
Answering medical enquiries.
Filing of cases and source
documentation.
And many more………
Causes of Adverse Events
Primary Pharmacology.
Secondary Pharmacology.
Physicochemical nature of compound.
Projects Handled
Appendix 1: Brief overview of
Pharmacovigilance Work flow.
Case processing
Case in
Data Entry
Data Review
Medical Review
Quality Review